Eben L Rosenthal

University of Alabama at Birmingham, Birmingham, Alabama, United States

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Publications (163)334.66 Total impact

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    ABSTRACT: Antibody-based photodynamic therapy-photoimmunotherapy (PIT)-is an ideal modality to improve cancer treatment because of its selective and tumor-specific mode of therapy. Because the use of PIT for cancer treatment is continuing to be described, there is great need to characterize a standardized light source for PIT application. In this work, we designed and manufactured a light-emitting diode (LED)/PIT device and validated the technical feasibility, applicability, safety, and consistency of the system for cancer treatment.
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 10/2014;
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    ABSTRACT: Background: Advanced cutaneous squamous cell carcinoma (cSCC) is an uncommon and aggressive malignancy. As a result, there is limited understanding of its biology and pathogenesis. CD147 and EGFR have been identified as oncologically important targets, but their relationship remains undefined in cSCCMethods: Multiple cSCC cell lines (Colo-16, SRB-1, and SRB-12), were treated in vitro with a range of chimeric anti-CD147 monoclonal antibody (mAb) (0, 50, 100, 200 µg/mL) or transfected with a small interfering RNA against CD147 (SiCD147). Cell proliferation, migration (scratch wound healing assay), and protein expression was then assessed. In vivo, Colo-16 flank xenografts were treated anti-CD147 mAb (150µg i.p. triweekly).Results: Following treatment with anti-CD147 (200 µg/mL), there was a significant decrease in proliferation for all cell lines relative to control (p<0.005). In addition, treatment with anti-CD147 (200 µg/mL) resulted in decreased cell migration for all cell lines, with an average of 43% reduction in closure compared to controls (p< 0.001). Colo-16 SiCD147 expression demonstrated similar reduction in proliferation and wound closure. Anti-CD147 antibody therapy and siRNA mediated reduction in CD147 expression were both found to decrease protein expression of EGFR which correlated with a reduction in downstream total and pAKT. Tumor growth in vivo was reduced for both the anti-CD147 treatment group and the SiCD147 group relative to controls.Conclusions: Inhibition and down-regulation of CD147 in cSCC resulted in suppression of the malignant phenotype in vitro and in vivo which may be mediated in part by an alteration in EGFR expression. As a result, CD147 may serve as a potential therapeutic target for advanced cSCC. Head Neck, 2014
    Head & Neck 10/2014; · 2.83 Impact Factor
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    ABSTRACT: Objectives/HypothesisTo compare the clinical and cost outcomes of transoral robotic surgery (TORS) versus open procedures following the U.S. Food and Drug Administration approval in December 2009.Study DesignRetrospective analysis of the Nationwide Inpatient Sample from 2008 to 2011.Methods Elective partial pharyngectomies and partial glossectomies for neoplasm were identified by International Classification of Diseases, 9th Revision, Clinical Modification code.ResultsTORS represented 2.1% in 2010 and 2.2% in 2011 of all transoral ablative procedures. Patients undergoing open partial pharyngectomy for oropharyngeal neoplasms (n = 1426) had more severe illness compared to TORS (n = 641). However, after controlling for minor-to-moderate severity of illness, open partial pharyngectomy was associated with longer hospital stay (5.2 vs. 3.7 days, P < 0.001), higher charge ($98,228 vs. $67,317, P < 0.001), higher cost ($29,365 vs. $20,706, P < 0.001), higher rates of tracheostomy and gastrostomy tube placement, and more wound and bleeding complications. TORS was associated with a higher rate of dysphagia (19.5% vs. 8.0%, P < 0.001). The lower cost of TORS remained significant in the major-to-extreme severity of illness group but was associated with higher complication rates when compared to open cases of the same severity of illness. A similar analysis of TORS partial glossectomy for base of tongue tumors had similar cost and length of stay benefits, whereas TORS partial glossectomy for anterior tongue tumors revealed longer hospital stays and no benefit in charge or cost compared to open.Conclusions Early data demonstrate a clinical and cost benefit in TORS partial pharyngectomy and partial glossectomy for the base of tongue but no benefit in partial glossectomy of the anterior tongue. It is likely that anatomic accessibility and extent of surgery factor into the effectiveness of TORS.Level of Evidence2c. Laryngoscope, 2014
    The Laryngoscope 08/2014; · 1.98 Impact Factor
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    ABSTRACT: The use of receptor-targeted antibodies conjugated to fluorophores is actively being explored for real-time imaging of disease states; however, the toxicity of the bioconjugate has not been assessed in non-human primates.
    Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 07/2014; · 2.47 Impact Factor
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    ABSTRACT: (1) Investigate oncologic survival outcomes and (2) analyze the impact of human papillomavirus status on prognosis in patients with oropharyngeal squamous cell carcinoma treated with transoral robotic versus open surgery.
    Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 07/2014;
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    ABSTRACT: To determine the tolerability and efficacy of long-term treatment with erlotinib for head and neck squamous cell carcinoma after salvage surgery.
    Annals of Surgical Oncology 07/2014; · 4.12 Impact Factor
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    ABSTRACT: Microvascular free tissue transfer is used for complex composite tissue defects in previously treated fields, in particular after treatment of malignant disease. The increasing incidence of skin cancer in the general population has increased the number of patients with massive tumors that require the expertise of the free flap reconstructive surgeon. We herein examine a number of the recent advances in the field that use free tissue transfer for orbitomaxillary and scalp reconstruction, including maxillary reconstruction, virtual surgical planning in head and neck reconstruction, and scalp reconstruction. Advanced computer algorithms allow planning of these procedures at a savings of time and cost. Free tissue transfer is a reconstructive modality that is often at the top of the reconstructive ladder and, in some instances, is the reconstructive method of choice. The ability to harvest composite tissue that matches the tissue defect in composition, surface area, and volume makes free tissue transfer a versatile modality.
    JAMA facial plastic surgery. 07/2014;
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    ABSTRACT: To investigate panitumumab–IRDye800 as an intraoperative optical imaging agent for epidermal growth factor receptor (EGFR)-expressing cancers, we developed clinical-quality panitumumab–IRDye800 and evaluated its specificity and sensitivity to visualize tumors by fluorescence imaging in a variety of mouse xenograft models with different levels of EGFR-expression. Panitumumab was chemically conjugated to NIR-dye (Li-COR 800CW) at well-defined and limited substitution ratio (1:1–2) for the characterization of fluorescence signals. The yield and purity of the conjugate was 80 ± 5% and 95 ± 2%, respectively (n = 6). Quality control (QC) tests showed that the product was suitable for clinical development. Female athymic nude xenograft tumor bearing mice (n = 5 per tumor model) with very low (BT-474), moderate (MDA-MB-231), and high (MDA-MB-468) EGFR-expression levels were administered panitumumab–IRDye800 formulations (100 μg of mAb in 100 μL of 0.9% saline) via tail-vein injection. Animal imaging and biodistribution experiments were conducted on an FMT 2500 (Perkin Elmer) fluorescence scanner at 24, 48, 72, 96, and 144 hours post-injection. Immuno-fluorescence images of a panitumumab–IRDye conjugate recorded in mouse xenograft models showed a good correlation (R2 = 0.91) between EGFR-expression level and tumor uptake. Uptake of panitumumab labeled with IR-Dye or [89Zr] in different tumor xenografts with high, medium, and low EGFR expression, as measured by fluorescence or radioactive counts, is highly correlated (r2 = 0.99). This preclinical in vivo study proved that panitumumab–IRDye800 is specific and optical imaging in conjunction with this probe is sensitive enough to detect EGFR-expressing tumors.
    Medicinal Chemistry Communication 07/2014; · 2.72 Impact Factor
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    ABSTRACT: Although mainly developed for preclinical research and therapeutic use, antibodies have high antigen specificity, which can be used as a courier to selectively deliver a diagnostic probe or therapeutic agent to cancer. It is generally accepted that the optimal antigen for imaging will depend on both the expression in the tumor relative to normal tissue and the homogeneity of expression throughout the tumor mass and between patients. For the purpose of diagnostic imaging, novel antibodies can be developed to target antigens for disease detection, or current FDA-approved antibodies can be repurposed with the covalent addition of an imaging probe. Reuse of therapeutic antibodies for diagnostic purposes reduces translational costs since the safety profile of the antibody is well defined and the agent is already available under conditions suitable for human use. In this review, we will explore a wide range of antibodies and imaging modalities that are being translated to the clinic for cancer identification and surgical treatment.
    Cancer and metastasis reviews 06/2014; · 7.79 Impact Factor
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    ABSTRACT: We sought to determine the safety and utility of Harmonic Scalpel-assisted free-flap harvesting as an alternative to a combined electrocautery and surgical clip technique. The medical records of 103 patients undergoing radial forearm free-flap reconstruction (105 free flaps) for head and neck surgical defects between 2006 and 2008 were reviewed. The use of bipolar electrocautery and surgical clips for division of small perforating vessels (n = 53) was compared to ultrasonic energy (Harmonic Scalpel; Ethicon Endo-Surgery, Inc., Cincinnati, Ohio) (n = 52) free-tissue harvesting techniques. Flap-harvesting time was reduced with the use of the Harmonic Scalpel when compared with electrocautery and surgical clip harvest (31.4 vs. 36.9 minutes, respectively; p = 0.06). Two patients who underwent flap harvest with electrocautery and surgical clips developed postoperative donor site hematomas, whereas no donor site complications were noted in the Harmonic Scalpel group. Recipient site complication rates for infection, fistula, and hematoma were similar for both harvesting techniques (p = 0.77). Two flap failures occurred in the clip-assisted radial forearm free-flap harvest group, and none in the Harmonic Scalpel group. Median length of hospitalization was significantly reduced for patients who underwent free-flap harvest with the Harmonic Scalpel when compared with the other technique (7 vs. 8 days; p = 0.01). The Harmonic Scalpel is safe, and its use is feasible for radial forearm free-flap harvest.
    Ear, nose, & throat journal 06/2014; 93(6):E36-E39. · 1.03 Impact Factor
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    ABSTRACT: Introduction: Proteins conjugated to the near infrared (NIR) moieties for detection of head and neck cancers are being translated to the clinic. However, little is known about the fluorescent properties of IRDye800CW after conjugation to antibodies. We investigated factors that may alter the real-time observed fluorescence of antibody conjugated dye and the rate of fluorescent signal loss. Methods: Signal loss was examined using three FDA approved monoclonal antibodies conjugated to IRDye800CW (LICOR) over a period of 15 days. Temperature effects on fluorescence were examined for conjugated dye in both solution and a mouse tumor model. Samples were cooled to -20°C then warmed to predetermined temperatures up to 60°C with imaging performed using the PEARL Impulse (LI-COR) and LUNA (Novadaq) systems. Results: Short term fluorescent signal loss (< 1 hour) was linear, while long term loss (15 days) was exponential with significant increases in rate observed with light exposure and increased temperatures. Cooling of tumor tissue at -20°C was shown to significantly increase tumor fluorescence on both imaging modalities when compared to room temperature (p=0.008, p=0.019). Concurrently the ratio of tumor to background fluorescent signal (TBR) increased with decreasing temperature with statistically significant increases seen at -20°C and 4°C (p=0.0015, p=0.03). Conclusions: TBR is increased with decreasing sample temperature, suggesting that the clinical exam of fluorescently labeled tissues may be improved at cooler temperatures. Our results indicate that both the rate of signal loss and the change in fluorescence with temperature observed for IRDye800CW are independent of the conjugating antibody.
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    ABSTRACT: Evaluate characteristics and risk factors for patients with advanced cutaneous squamous cell carcinoma (cSCC). Retrospective case series. Tertiary care center. Chart review of patients with cSCC undergoing a parotidectomy (2003-2012). Of 218 patients identified, 49% presented with a new primary lesion (n = 107) and 51% with a recurrence (n = 111). Parotid lymph nodes were positive in 52% of patients; 81% had a concurrent neck dissection, and 28% had cervical lymph node metastases. In 18% of patients, both parotid and cervical nodes were positive, while 44% were both parotid and cervical node negative; 33% had positive parotid and negative cervical nodes, and only 5% had negative parotid and positive cervical nodes. The overall 2- and 5-year survival rates were 0.71 and 0.58. Overall 5-year survival was lower for patients presenting with recurrent (0.49) versus new primary disease (0.69; P = .04). In addition, decreased overall 5-year survival rates were associated with cervical lymph node involvement (0.47 vs. 0.62; P = .01). There was no difference in overall survival when stratified by parotid lymph node involvement (P = .85), margin status (P = .67), perineural invasion (P = .42), facial nerve sacrifice (P = .92), or type of parotid operation performed (P = .51). In this study, cervical, but not parotid, lymph node involvement was associated with poor outcomes in patients with advanced cSCC requiring a parotidectomy. In patients without evidence of cervical or parotid lymph node involvement, a neck dissection may be spared, given there is a 5% chance of occult disease.
    Otolaryngology Head and Neck Surgery 01/2014; · 1.73 Impact Factor
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    ABSTRACT: Microbubbles triggered with localized ultrasound (US) can improve tumor drug delivery and retention. Termed US-stimulated drug delivery, this strategy was applied to head and neck cancer (HNC) in a post-surgical tumor resection model. Luciferase-positive HNC squamous cell carcinoma (SCC) was implanted in the flanks of nude athymic mice (N = 24) that underwent various degrees of surgical tumor resection (0%, 50% or 100%). After surgery, animals received adjuvant therapy with cetuximab-IRDye alone, or cetuximab-IRDye in combination with US-stimulated drug delivery or saline injections (control) on days 4, 7 and 10. Tumor drug delivery was assessed on days 0, 4, 7, 10, 14 and 17 with an in vivo fluorescence imaging system, and tumor viability was evaluated at the same times with in vivo bioluminescence imaging. Tumor caliper measurements occurred two times per week for 24 d. Optical imaging revealed that in the 50% tumor resection group, US-stimulated drug delivery resulted in a significant increase in cetuximab delivery compared with administration of drug alone on day 10 (day of peak fluorescence) (p = 0.03). Tumor viability decreased in all groups that received cetuximab-IRDye in combination with US-stimulated drug delivery, compared with the group that received only the drug. After various degrees of surgical resection, this novel study reports positive improvements in drug uptake in the residual cancer cells when drug delivery is stimulated with US.
    Ultrasound in medicine & biology 01/2014; · 2.46 Impact Factor
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    ABSTRACT: Various case reports on nasal myiasis written during the 1990s and 2000s state that nasal myiasis, which is known as peenash among South Asian natives, is a form of divine punishment in Hindu mythology, but do not provide citations from Hindu scriptures that would suggest this interpretation. This paper aims to discuss the phenomenon of peenash in a historical context by examining medical literature written during the nineteenth and early twentieth centuries, to identify Hindu texts contributing to the belief of some Hindus that nasal myiasis is a form of divine punishment, and to provide an overview of contemporary treatment for and management of nasal myiasis.
    Journal of Religion and Health 01/2014; · 1.02 Impact Factor
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    ABSTRACT: Background Previous IONM studies have demonstrated modest-to-no benefit and did not include a nationwide sample of hospitals representative of broad thyroidectomy practices. This national study was designed to compare vocal cord paralysis (VCP) rates between thyroidectomy with IONM and without monitoring (Conventional). Study Design We performed a retrospective analysis of 243,527 thyroidectomies during 2008-2011 using the Nationwide Inpatient Sample. Results IONM utilization increased throughout the study period (2.6%, 5.6%, 6.1%, 6.9%) and during this time, VCP rates in the IONM group initially increased year-over-year [0.9%(2008), 2.4%(2009), 2.5%(2010), 1.4%(2011)]. In unadjusted analyses, IONM was associated with significantly higher VCP rates (Conventional 1.4% vs IONM 1.9%, p<0.001). After propensity score matching, IONM remained associated with higher VCP rates in partial thyroidectomy and lower VCP rates for total thyroidectomy with neck dissection. Hospital-level analysis revealed that VCP rates were not explained by differential laryngoscopy rates, decreasing the likelihood of ascertainment bias. Additionally, for hospitals where IONM was applied to >50% of thyroidectomies, lower VCP rates were observed (1.1%) compared to hospitals that applied IONM to <50% (1.6%,p=0.016). Higher hospital volume correlated with lower VCP rates in both groups (<75, 75-299, >300 thyroidectomies/year: IONM-2.1%, 1.7%, 1.7%, conventional-1.5%, 1.3%, 1.0%). Conclusions According to this study, IONM has not been broadly adopted into practice. Overall, IONM was associated with a higher rate of VCP even after correction for numerous confounders. In particular, low institutional utilization of IONM and use in partial thyroidectomies is associated with higher rates of VCP. Further studies are warranted to support the broader application of IONM in patients where benefit can be reliably achieved.
    Journal of the American College of Surgeons 01/2014; · 4.50 Impact Factor
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    ABSTRACT: IMPORTANCE Pharyngocutaneous fistula formation after pharyngeal reconstruction is one of the most common and challenging problems to manage. Despite many advances in management, the published success rates indicate a role for any adjuvant therapy that could potentially decrease this complication. OBJECTIVE To describe the use of intraluminal negative pressure dressings (NPDs) in pharyngeal reconstruction. DESIGN, SETTING, AND PARTICIPANTS Retrospective case series at a tertiary care academic hospital. Twelve laryngectomy patients underwent pharyngeal reconstruction augmented by placement of an intrapharyngeal NPD in combination with the introduction of vascularized tissue from August 2011 to May 2012. All patients had potential risk factors for compromised wound healing defined as previous radiation therapy, hypothyroidism, diabetes mellitus, compromised nutrition, or established pharyngocutaneous fistula. INTERVENTIONS An NPD was placed in an intraluminal position spanning the length of the pharyngeal defect as part of the reconstructive procedure. The negative pressure sponge was attached to a standard nasogastric tube to which negative pressure was applied. External closure of the pharynx was then achieved with regional or free tissue transfer. MAIN OUTCOMES AND MEASURES Pharyngeal closure rates, timing until return to oral diet, identification of wound healing risk factors, and adverse events related to use of the device. RESULTS Eleven of 12 patients (92%) achieved pharyngeal closure with reconstruction using negative pressure wound therapy. All patients had at least 1 potential risk factor for compromised wound healing, with 11 of 12 (92%) having 2 or more. Seven patients had an established pharyngocutaneous fistula, and 5 patients underwent primary reconstruction after laryngopharyngectomy. In 6 of these 7 patients undergoing fistula repair, pharyngeal closure was achieved, and they resumed an oral diet at 1 week postoperatively. The other had successful leak repair initially, but 1 week later developed a separate area of wound breakdown and a second fistula. All 5 patients in whom an intraluminal NPD was placed at the time of initial vacularized tissue reconstruction were able to resume an oral diet by 3 weeks postoperatively, with 3 of them eating by mouth at 1 week postoperatively. No serious adverse events could be attributed to the use of intraluminal NPDs. CONCLUSIONS AND RELEVANCE Intraluminal negative pressure wound therapy is feasible and safe. Future research should be conducted to determine its potential in optimizing pharyngeal reconstruction in high-risk patients.
    JAMA otolaryngology-- head & neck surgery. 12/2013;
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    ABSTRACT: IMPORTANCE Negative pressure wound therapy has been shown to accelerate healing. There is a paucity of literature reporting its use as a tool to promote wound healing in head and neck reconstruction. OBJECTIVE To review 1 institution's experience with negative pressure dressings to further describe the indications, safety, and efficacy of this technique in the head and neck. DESIGN, SETTING, AND PARTICIPANTS Retrospective case series at a tertiary care academic hospital. One hundred fifteen patients had negative pressure dressings applied between April 2005 and December 2011. Data were gathered, including indications, details of negative pressure dressing use, adverse events, wound healing results, potential risk factors for compromised wound healing (defined as previous radiation therapy, hypothyroidism, or diabetes mellitus), and wound characteristics (complex wounds included those with salivary contamination, bone exposure, great vessel exposure, in the field of previous microvascular free tissue transfer, or in the case of peristomal application in laryngectomy). EXPOSURE Negative pressure wound therapy utilized after head and neck reconstruction. MAIN OUTCOMES AND MEASURES Indications for therapy, length and number of dressing applications, identification of wound healing risk factors, classification of wound complexity, wound healing results, and adverse events related to the use of the device. RESULTS Negative pressure wound therapy was used primarily for wounds of the neck (94 of 115 patients [81.7%]) in addition to other head and neck locations (14 of 115 patients [12.2%]), and free tissue transfer donor sites (7 of 115 patients [6.1%]). The mean (SD) wound size was 5.6 (5.0) cm. The mean number of negative pressure dressing applications was 1.7 (1.2), with an application length of 3.7 (1.4) days. Potential risk factors for compromised wound healing were present in 82 of 115 patients (71.3%). Ninety-one of 115 patients (79.1%) had complex wounds. Negative pressure dressings were used in wounds with salivary contamination (n = 64), bone exposure (n = 40), great vessel exposure (n = 25), previous free tissue transfer (n = 55), and peristomal application after laryngectomy (n = 32). Adverse events occurred in 4 of 115 patients (3.5%). CONCLUSIONS AND RELEVANCE Negative pressure wound therapy in head and neck surgery is safe and has potential to be a useful tool for complex wounds in patients with a compromised ability to heal. LEVEL OF EVIDENCE 4.
    JAMA facial plastic surgery. 12/2013;
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    ABSTRACT: Complete surgical resection of breast cancer is a powerful determinant of patient outcome, and failure to achieve negative margins results in reoperation in between 30% and 60% of patients. We hypothesize that repurposing Food and Drug Administration-approved antibodies as tumor-targeting diagnostic molecules can function as optical contrast agents to identify the boundaries of malignant tissue intraoperatively. The monoclonal antibodies bevacizumab, cetuximab, panitumumab, trastuzumab, and tocilizumab were covalently linked to a near-infrared fluorescence probe (IRDye800CW) and in vitro binding assays were performed to confirm ligand-specific binding. Nude mice bearing human breast cancer flank tumors were intravenously injected with the antibody-IRDye800 bioconjugates and imaged over time. Tumor resections were performed using the SPY and Pearl Impulse systems, and the presence or absence of tumor was confirmed by conventional and fluorescence histology. Tumor was distinguishable from normal tissue using both SPY and Pearl systems, with both platforms being able to detect tumor as small as 0.5 mg. Serial surgical resections demonstrated that real-time fluorescence can differentiate subclinical segments of disease. Pathologic examination of samples by conventional and optical histology using the Odyssey scanner confirmed that the bioconjugates were specific for tumor cells and allowed accurate differentiation of malignant areas from normal tissue. Human breast cancer tumors can be imaged in vivo with multiple optical imaging platforms using near-infrared fluorescently labeled antibodies. These data support additional preclinical investigations for improving the surgical resection of malignancies with the goal of eventual clinical translation.
    Journal of Surgical Research 11/2013; · 2.02 Impact Factor
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    ABSTRACT: Objective Identifying risk factors for hardware removal in patients undergoing mandibular reconstruction with vascularized osseous free flaps remains a challenge. The purpose of this study is to identify potential risk factors, including osteocutaneous radial forearm versus fibular flap, for need for removal and to describe the fate of implanted hardware.Study DesignCase series with chart reviewSettingAcademic tertiary care medical center.Subjects and Methods Two hundred thirteen patients undergoing 227 vascularized osseous mandibular reconstructions between the years 2004 and 2012. Data were compiled through a manual chart review, and patients incurring hardware removals were identified.ResultsThirty-four of 213 evaluable vascularized osseous free flaps (16%) underwent surgical removal of hardware. The average length of time to removal was 16.2 months (median 10 months), with the majority of removals occurring within the first year. Osteocutaneous radial forearm free flaps (OCRFFF) incurred a slightly higher percentage of hardware removals (9.9%) compared to fibula flaps (6.1%). Partial removal was performed in 8 of 34 cases, and approximately 38% of these required additional surgery for removal.Conclusion Hardware removal was associated with continued tobacco use after mandibular reconstruction (P = .03). Removal of the supporting hardware most commonly occurs from infection or exposure in the first year. In the majority of cases the bone is well healed and the problem resolves with removal.
    Otolaryngology Head and Neck Surgery 11/2013; · 1.73 Impact Factor
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    ABSTRACT: Aberrant overexpression and/or activation of epidermal growth factor receptor (EGFR) is associated with many types of cancers. EGFR variant III (EGFRvIII) is a common in-frame deletion mutant, which lacks a large part of the extracellular portion (exons 2-7), including components of the ligand-binding domain. Although EGFR has been extensively studied as a molecular imaging target, information about EGFRvIII-targeted molecular imaging is lacking. In this study, the EGFR-specific affibody, therapeutic antibody panitumumab and ligand EGF were labeled with IRDye 800CW (Ex/Em: 774/789 nm), yielding Aff800, Pan800 and EGF800, respectively. The binding affinities of the labeled agents were compared in cell-based assays using a rat glioma cell line F98 parental (F98-p) lacking EGFR expression, and two F98-derived transgenic cell lines expressing EGFR or EGFRvIII (designated as F98-EGFR and F98-vIII, respectively). Results showed that all agents could bind to F98-EGFR, with Pan800 having the highest binding affinity, followed by Aff800 and EGF800. Pan800 and Aff800, but not EGF800, also bound to F98-vIII. In vivo animal imaging demonstrated that compared to F98-p tumors, F98-EGFR tumors generated higher signals with all three agents. However, in the case of F98-vIII, only Pan800 and Aff800 signals were higher. Analysis of tissue lysates showed that a large portion of Pan800 was degraded into small fragments in F98-EGFR and F98-vIII tumors, possibly due to proteolytic digestion after its specific binding and internalization. In conclusion, Pan800 and Aff800 could be used as imaging agents for both wild type EGFR and EGFRvIII, whereas EGF800 only targets wild type EGFR.
    Cancer biology & therapy 10/2013; 15(2). · 3.29 Impact Factor

Publication Stats

1k Citations
334.66 Total Impact Points


  • 2001–2014
    • University of Alabama at Birmingham
      • • Department of Surgery
      • • Division of Otolaryngology, Head and Neck Surgery
      Birmingham, Alabama, United States
  • 2013
    • Florida Hospital Celebration
      Celebration, Florida, United States
  • 2011–2013
    • University of Texas MD Anderson Cancer Center
      • Department of Plastic Surgery
      Houston, TX, United States
    • University of Washington Seattle
      Seattle, Washington, United States
    • Hospital del Trabajador de Santiago
      CiudadSantiago, Santiago, Chile
    • University Center Rochester
      Rochester, Minnesota, United States
  • 2012
    • University of Alabama
      • Department of Surgery
      Tuscaloosa, Alabama, United States
  • 2007–2012
    • Oregon Health and Science University
      • Department of Otolaryngology, Head & Neck Surgery
      Portland, OR, United States
  • 2010
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia
  • 2008
    • The Australian Society of Otolaryngology Head & Neck Surgery
      Evans Head, New South Wales, Australia
  • 2006
    • University of Iowa
      • Department of Otolaryngology-Head and Neck Surgery
      Iowa City, IA, United States